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Abstract Background Obstructive sleep apnoea (OSA) is a sleep-disordered breathing characterized by intermittent hypoxia (IH) that may cause cognitive dysfunction. However, the impact of IH on molecular processes involved in cognitive function remains unclear. Methods C57BL / 6 J mice were exposed to either normoxia (control) or IH for 6 weeks. DNA hydroxymethylation was quantified by hydroxymethylated DNA immunoprecipitation (hMeDIP) sequencing. ten-eleven translocation 1 (Tet1) was knocked down by lentivirus. Specifically, cognitive function was assessed by behavioral experiments, pathological features were assessed by HE staining, the hippocampal DNA hydroxymethylation was examined by DNA dot blot and immunohistochemical staining, while the Wnt signaling pathway and its downstream effects were studied using qRT-PCR, immunofluorescence staining, and Luminex liquid suspension chip analysis. Results IH mice showed pathological changes and cognitive dysfunction in the hippocampus. Compared with the control group, IH mice exhibited global DNA hydroxylmethylation in the hippocampus, and the expression of three hydroxylmethylases increased significantly. The Wnt signaling pathway was activated, and the mRNA and 5hmC levels of Wnt3a, Ccnd2, and Prickle2 were significantly up-regulated. Further caused downstream neurogenesis abnormalities and neuroinflammatory activation, manifested as increased expression of IBA1 (a marker of microglia), GFAP (a marker of astrocytes), and DCX (a marker of immature neurons), as well as a range of inflammatory cytokines (e.g. TNFa, IL3, IL9, and IL17A). After Tet1 knocked down, the above indicators return to normal. Conclusion Activation of Wnt signaling pathway by hippocampal Tet1 is associated with cognitive dysfunction induced by IH. Graphical Abstract

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Background Numerous investigations have examined the potential link between allergic rhinitis (AR) and attention deficit hyperactivity disorder (ADHD). However, some studies show no association between the two diseases. The connection between these two conditions remains inconclusive. This study aimed to conduct a meta-analysis exploring the correlation between AR and ADHD. Methods We conducted systematic searches of the MEDLINE, EMBASE, Cochrane Library, ERIC, PubMed, Web of Science, and CINAHL databases, up to the year 2023. Subsequently, we conducted a meta-analysis using R 4.2.2, where we computed the pooled odds ratio with a 95% confidence interval to assess the relationship between AR and ADHD within studies exhibiting similar characteristics. Statistical heterogeneity was evaluated by computing the value using the Cochrane Intervention Manual’s guidelines. Additionally, subgroup analyses were conducted by stratifying the study population according to gender, age, etc. Sensitivity analysis was performed by systematically removing individual studies. Results In this systematic review, we incorporated 12 eligible studies, collectively encompassing a sample size of 530,360 participants. Within the included studies, heterogeneity was observed, and the utilization of a random-effects model demonstrated a noteworthy correlation between children with ADHD and the presence of AR. Similarly, children with AR exhibited a significant correlation with the occurrence of ADHD. We also found some relationships in subgroup analyses. Conclusion A substantial correlation is evident between AR and ADHD in children and adolescents. AR may potentially contribute as a risk factor for the onset of ADHD, and conversely, ADHD may heighten the likelihood of developing AR.

BackgroundAllergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood.MethodsWe used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment.ResultsWe showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway.ConclusionTogether, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 3 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Our analysis identified and quantified 2699 Kac sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant down-regulation of proteins that are known to be involved in endocrine hormone secretion. This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus as well as its potential role in endocrine impairment.

Summary: Disorders of folic acid metabolism during pregnancy lead to fetal neural tube defects (NTDs). However, the mechanisms still require further investigation. Here, we aim to analyze the brain metabolic profiles of 30 NTDs and 30 healthy fetuses. Our results indicated that low-folate diet during early life played a causal role in cerebral metabolism, especially in lipometabolic disturbance, highlighting the importance of folate in modulating brain development and metabolism. Next, we established a mouse model of NTDs. Interestingly, the differential metabolites are mainly involved in glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids both in human and mice fetal brain. Since intestinal microbes could critically regulate neurofunction via the intestinal-brain axis, we further found the abundances of Firmicutes and Bacteroidetes in the gut of pregnant mice were correlated with the abundances of lipid metabolism related metabolites in the fetal brain. This finding probably reflects the intergenerational microbial-metabolism biomarkers of NTDs.

PurposeOlfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients.Methods23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The “Sniffin’ Sticks” was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA).ResultsA decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1α, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship.ConclusionThe disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6A shows a definite cell-specific methylation profile and m6A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway.

Abstract Background We aimed to perform a systematic review and meta-analysis of the association between obstructive sleep apnea (OSA) and cardiac as well as coronary impairment evaluated using imaging modalities. Finding of this study will provide more robust evidence regarding OSA-induced cardiovascular damage. Methods We systematically searched through PubMed, EMBASE, and Cochrane library databases for relevant literatures on the association between OSA and cardiovascular damage evaluated using imaging modalities, and manually searched the references of selected articles for additional relevant articles. For each clinical parameter relevant to the meta-analysis, we first evaluated the methodological heterogeneity of the relevant studies and thereafter pooled the data together using fixed effect or random effect model. The difference in the relevant indices of cardiovascular damage between OSA patients and controls was evaluated using the standardized mean difference. Results Of the 82 articles included in the final systematic analysis, 20 studies explored the association between OSA and coronary atherosclerosis. OSA patients had higher rate of coronary atherosclerosis assessed by coronary artery calcification score and plaque volume. Moreover, the severity of OSA and coronary atherosclerosis displayed a positive correlation. The rest of the studies (n = 62) evaluated cardiac alterations in OSA patients. According to the inclusion and exclusion criteria, 46 studies yielding 3082 OSA patients and 1774 controls were pooled for the meta-analysis. For left cardiac structure and function, OSA patients exhibited significantly wider left atrial diameter; higher left atrium volume index; wider left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and left ventricular mass; higher left ventricular mass index; wider interventricular septum diameter and posterior wall diameter; and higher left ventricular myocardial performance index (all p

BackgroundOlfaction is one of the five basic senses of human beings. As such, olfactory dysfunction seriously affects patients' quality of life and can even endanger them. In recent years, olfactory dysfunction has attracted greater research interest, and numerous studies have been published on olfactory dysfunction. However, there are few studies on olfactory dysfunction through bibliometric analysis. This study aims to describe the current situation and identify the foci and potential new research directions of olfactory dysfunction using a bibliometric approach.MethodsArticles related to olfactory dysfunction published from 2002 to 2021 were located in the Web of Science Core Collection of Clarivate Analytics (London, UK). Bibliometric analyses were conducted with the CiteSpace (Chaomei Chen, Drexel University, Philadelphia, PA, USA) and VOSviewer (Center for Science and Technology Studies, Leiden University, Leiden, Netherlands) software programs.ResultsThe number of articles published each year showed an upward trend, especially in 2020, where a sharp increase had occurred due to the coronavirus disease 2019 (COVID-19) pandemic. The United States was the country with the most publications and the strongest international cooperation. In terms of institutions, the greatest number of publications from a single institution came from Dresden University of Technology. Thomas Hummel was the author who had contributed the most articles. An analysis of co-citation networks and burst keywords in the field revealed a shift from “gonadotropin-releasing hormone” and “apoptosis” earlier on to “olfactory training,” “COVID-19,” and “Parkinson's disease” more recently. “Outcome,” “COVID-19,” “infection,” and “pathogenesis” are topics of the research frontier and hotspots.ConclusionMore attention has been paid to olfactory dysfunction as the understanding of it has improved in the past 20 years. This study provides researchers with an objective, systematic, and comprehensive analysis of the literature on olfactory dysfunction. The current frontier areas and hotspots in the field focus on the pathological mechanisms of olfactory dysfunction after infection with COVID-19 and its different prognoses. The pathophysiological mechanism of olfactory dysfunction in neurodegenerative diseases and COVID-19 will be a primary future research direction.

Electrophoretic microswimmers aren’t well suited to function in vivo because electric-field screening reduces their speed in higher ionic-strength solutions. Here the authors propose a microswimmer that exploits high surface conductance to improve this ion tolerance to enable operation in a high salt environment.

The ability to direct microwimmers along a particular trajectory is advantageous for targeted drug delivery and manufacturing at the microscale. Here Zheng et al. use different types of light-absorbing dyes to enable selective activation of different microswimmers independently from each other.

Two-dimensional atomic crystals are known to be effective electrode materials for energy storage applications. Here, the authors report the preparation of various two-dimensional metal oxides, including those which do not have a layered parent structure, via a salt templating strategy.

Abstract Amidst the burgeoning field of cancer nanomedicine, dense extracellular matrices and anomalous vascular structures in the tumor microenvironment (TME) present substantial physical barriers to effective therapeutic delivery. These physical barriers hinder the optimal bioavailability of nanomedicine. Here, we propose a pioneering dual-modal strategy for overcoming physical barriers via soft organosilica nanocapsules (SMONs). Hyaluronidase-modified flexible spheres work by degrading the extracellular matrix and utilizing their flexible characteristics to enhance penetration into deeper layers. Compared with their stiff counterparts, the SMONs show diminished Young’s modulus, then the inherent softness of the SMONs confers distinct advantages, and significantly augmented cellular internalization within 4T1 cells, leading to an amplified in vitro photodynamic therapeutic effect. Furthermore, hyaluronidase-functionalized SMONs (SMONs-HAase) exhibit enhanced tumor penetration in 3D spheroids. Post incorporation of the photosensitizer chlorin e6, when administered intravenously, these soft organosilica nanocapsules amplify the efficacy of photodynamic therapy. In addition, RNA-seq analysis of SMONs-HAase-Ce6 shows it alters gene expression, degrading the extracellular matrix and impairing mitochondrial function. To sum up, this work elucidates the potential of a dual-modal strategy, highlighting the promise of SMONs in overcoming TME physical barriers and optimizing therapeutic outcomes. Graphical abstract

Abstract In agroecosystems, nitrous oxide (N₂O) emissions are influenced by both microbiome composition and soil properties, yet the relative importance of these factors in determining differential N₂O emissions remains unclear. This study investigates the impacts of these factors on N₂O emissions using two primary agricultural soils from northern China: fluvo-aquic soil (FS) from the North China Plain and black soil (BS) from Northeast China, which exhibit significant differences in physicochemical properties. In non-sterilized controls (NSC), we observed distinct denitrifying bacterial phenotypes between FS and BS, with BS exhibiting significantly higher N₂O emissions. Cross-inoculation experiments were conducted by introducing extracted microbiomes into sterile recipient soils of both types to disentangle the relative contributions of soil properties and microbiomes on N₂O emission potential. The results showed recipient-soil-dependent gas kinetics, with significantly higher N₂O/(N₂O + N₂) ratios in BS compared to FS, regardless of the inoculum type. Metagenomic analysis further revealed significant shifts in denitrification genes and microbial diversity of the inoculated bacteriomes influenced by the recipient soil. The higher ratios of nirS/nosZ in FS and nirK/nosZ in BS indicated that the recipient soil dictates the formation of different denitrifying guilds. Specifically, the BS environment fosters nirK-based denitrifiers like Rhodanobacter, contributing to higher N₂O accumulation, while FS supports a diverse array of denitrifiers, including Pseudomonas and Stutzerimonas, associated with complete denitrification and lower N₂O emissions. This study underscores the critical role of soil properties in shaping microbial community dynamics and greenhouse gas emissions. These findings highlight the importance of considering soil physicochemical properties in managing agricultural practices to mitigate N₂O emissions.

The active ingredient in traditional Chinese medicine, silybin (SBN), is known to inhibit the proliferation of cancer cells and synergistically enhance the anticancer effects of the chemotherapy drug doxorubicin (DOX). However, the combination of SBN and DOX faces challenges such as a lack of targeting, short half-lives, different administration routes, and pharmacokinetic processes, which prevent the drug combination from effectively targeting tumors and diminish their synergistic potential, thereby limiting their in vivo antitumor effects. In response, this study proposes the development of a novel nanocarrier system based on molybdenum disulfide (MoS₂) modified with polyethylene glycol (PEG) and sialic acid (SA) to co-deliver SBN and DOX. This system is designed to trigger the release of the drugs in response to dual stimuli of pH and near-infrared light, increasing the intracellular concentration of the drugs and enhancing their synergistic interaction. The MoS₂-LPN-SBN/DOX nanosystem circulates within the body and specifically accumulates at tumor sites due to the enhanced permeability and retention (EPR) effect and SA-mediated active targeting. Upon exposure to near-infrared light, the system provides combined chemo- and photothermal therapy, leading to significant tumor suppression. This research offers a new approach and strategy for the clinical treatment of lung cancer, suggesting a promising pathway for enhancing the efficacy of traditional therapies.

Abstract Neutrophilic inflammation contributes to multiple chronic inflammatory airway diseases, including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), and is associated with an unfavorable prognosis. Here, using single-cell RNA sequencing (scRNA-seq) to profile human nasal mucosa obtained from the inferior turbinates, middle turbinates, and nasal polyps of CRSwNP patients, we identify two IL-1 signaling-induced cell subsets—LY6D + club cells and IDO1 + fibroblasts—that promote neutrophil recruitment by respectively releasing S100A8/A9 and CXCL1/2/3/5/6/8 into inflammatory regions. IL-1β, a pro-inflammatory cytokine involved in IL-1 signaling, induces the transdifferentiation of LY6D + club cells and IDO1 + fibroblasts from primary epithelial cells and fibroblasts, respectively. In an LPS-induced neutrophilic CRSwNP mouse model, blocking IL-1β activity with a receptor antagonist significantly reduces the numbers of LY6D + club cells and IDO1 + fibroblasts and mitigates nasal inflammation. This study implicates the function of two cell subsets in neutrophil recruitment and demonstrates an IL-1-based intervention for mitigating neutrophilic inflammation in CRSwNP.

Weiningbeishan is located in the eastern section of the North Qilian orogenic belt, which is one of the regions with the most favorable conditions for cobalt mineralization in Ningxia. Objective To understand the formation conditions and mineralization regularity of cobalt deposits in this area, Methods this paper summarizes the geological characteristics, controlling factors, and spatiotemporal distribution patterns of typical associated cobalt deposits in Weiningbeishan based on detailed field investigations and previous exploration results and proposes future exploration directions. Results Research has shown that the Datonggou copper cobalt deposit, Chaliangzi iron cobalt deposit, and Tuyao iron cobalt deposit are currently three representative associated cobalt deposits discovered in Weiningbeishan area. Among them, three copper cobalt ore bodies were discovered in Datonggou, with the highest Co grade of 0.06%. Cobalt-bearing minerals mainly include pyroxenite, cobalt-bearing pyrite and cobalt-bearing limonite. There are 4 ore belts and 8 iron cobalt ore bodies are distributed in Chaliangzi, with the highest Co grade of 0.03%. The cobalt-bearing minerals are mainly cobalt-bearing limonite. Only one iron cobalt ore body was found in Tuyao, with the highest Co grade of 0.20%. The cobalt-bearing minerals are similar to those of Chaliangzi. Cobalt mineralization is evidently controlled by faults, with the western cobalt deposit mainly controlled by east-west faults and their combined control with northeast faults, while the eastern cobalt deposits are mainly controlled by north-south faults. Cobalt ore are mainly found in the Upper Carboniferous Tupo Formation, which was the main source strata. Lithological control is mainly observed at the "silica-calcium interface" and the lithological combination interface with different competence, which controlled the mineral precipitation. The cobalt metallogenic era was the Indosinian. Cobalt was closely related to Cu, Au, Fe and Mn. Cobalt related to Cu and Au were mainly distributed in the west, while cobalt related to Fe and Mn were mainly distributed in the east. The diversity of mineral species in this region may be attributed to the multistage superimposition of structures and hydrothermal activity. Conclusion The most favourable locations for identifying cobalt deposits are the east-west faults and their intersections with the northeast faults in the western part, the north-south Carboniferous and Devonian interface faults in the eastern part, the " silica-calcium interface " within the Tupo Formation, and the lithological combination interfaces with different competence. Malachite alteration and ferritization are the most important prospecting indicators for copper cobalt deposits and iron cobalt deposits.

Abstract Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.

This case report describes a 62-year-old male with a notable medical history, including surgically treated bladder cancer and the suspicion of metastatic disease. He underwent 18F-FDG PET/CT imaging as part of the initial diagnostic workup, which identified several marginally hypodense hepatic lesions. These lesions exhibited metabolic activity that was slightly lower than the surrounding hepatic parenchyma, raising concerns for metastatic involvement. Subsequent 18F-DOTATATE PET/CT imaging significantly expanded the diagnostic perspective by identifying multiple somatostatin receptor (SSTR)-positive lesions, not only in the liver but also in lymph nodes and bones. This marked an important diagnostic advancement over the initial FDG PET/CT findings, showcasing the superior sensitivity of 18F-DOTATATE PET/CT in detecting SSTR-expressing tumors. Pathological evaluation after these imaging studies confirmed the diagnosis of a rectal neuroendocrine tumor (NET) with extensive hepatic metastasis, altering the clinical management and therapeutic approach for the patient. This case underscores the pivotal role of integrating 18F-DOTATATE and FDG PET/CT in the diagnostic and therapeutic management of neuroendocrine tumors, highlighting the complementary nature of these imaging modalities. The findings advocate for the use of 18F-DOTATATE PET/CT in cases where NETs are suspected, particularly for its enhanced sensitivity in detecting SSTR-positive lesions across various sites, thereby facilitating a more comprehensive disease assessment and informed therapeutic planning.

68Ga-DOTA-TATE has been successfully applied in the diagnosis of clinical neuroendocrine tumors，but its short half-life limits its widespread use. This study aimed to develop [18F]AlF-NOTA-TATE to meet the clinical demands of patients with neuroendocrine tumors (NETs) for diagnosis and treatment evaluation. A new column chromatography purification method for [18F]AlF-NOTA-TATE was developed and automated synthesis was performed using a clinical single-vessel multi-functional fluorine synthesis module. The lipophilicity, in vitro stability，and pharmacokinetics of [18F]AlF-NOTA-TATE were studied，and biodistribution experiments and PET/CT imaging of nude mice with NCI-H69 (SSTR2 positive expression) small cell lung cancer were conducted，followed by preliminary clinical evaluation on three patients with neuroendocrine tumors. The new column chromatography purification method for [18F]AlF-NOTA-TATE was simple，which was synthesized in a short time with higher than 95% of radiochemical purity and，less than 3% of.ethanol content. Pharmacokinetic and biodistribution experiments in BALB/c mice showed rapid blood clearance of the drug and renal metabolism. PET/CT imaging of tumor-bearing mice showed specific uptake of the radiotracer in SSTR-positive tumors. Preliminary clinical application showed that [18F]AlF-NOTA-TATE is well targeted in patients with long retention time and can provide better image quality. The column chromatography method for the preparation of [18F]AlF-NOTA-TATE was simple and had high radiochemical purity. Preliminary clinical results suggested that [18F]AlF-NOTA-TATE has further value for clinical research.

Abstract In order to improve the measurement accuracy of mutual inductance parameters of transmission lines in the environment of double circuit power lines without power outage, this paper establishes simulation models for measuring mutual inductance parameters of transmission lines using the different frequency method in two modes: equal and unequal zero sequence self‐parameters of two circuit lines, using a parallel zero sequence coupling model of double circuit power lines. In the article, simulation analysis is conducted on the line parameters with a coupling coefficient between 0.4 and 0.6 and a line length of 20–50 km. In order to further verify the correctness of the simulation model and measurement methods, a test bench was established based on the principle of line mutual inductance parameter testing in a laboratory dual circuit line without a power outage environment for experimental testing. By comparing the test values under experimental conditions with the standard values, it has been proven that the model and method can meet the actual measurement requirements of engineering.

Introduction: Whole-genome duplication (WGD) is one of the most sudden and dramatic events rarely reported in invertebrates, but its occurrence can lead to physiological, morphological, and behavioral diversification. WGD has also never been reported in barnacles, which is one of the most unique groups of crustaceans with extremely speciallized morphology (calcareous shells) and habits (intertidal sessile lifestyle). Objectives: To investigate whether WGD has occurred in barnacles and examine its potential role in driving the adaptive evolution and diversification of barnacles. Methods: Based on a newly sequenced and assembled chromosome-level barnacle genome, a novel WGD event has been identified in barnacles through a comprehensive analysis of interchromosomal synteny, the Hox gene cluster, and synonymous substitution distribution. Results: We provide ample evidences for WGD in the barnacle genomes. Comparative genomic analysis indicates that this WGD event predates the divergence of Thoracicalcarea, occurring more than 247 million years ago. The retained ohnologs from the WGD are primarily enriched in various pathways related to environmental information processing, shedding light on the adaptive evolution and diversification of intertidal sessile lifestyle. In addition, transcriptomic analyses show that most of these ohnologs were differentially expressed following the ebb of tide. And the cytochrome P450 ohnologs with differential expression patterns are subject to subfunctionalization and/or neofunctionalization for intertidal adaptation. Besides WGD, parallel evolution underlying intertidal adaptation has also occurred in barnacles. Conclusion: This study revealed an ancient WGD event in the barnacle genomes, which is potentially associated with the origin and diversification of thoracican barnacles, and may have contributed to the adaptive evolution of their intertidal sessile lifestyle.

Purpose: Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients. Methods: 23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The "Sniffin' Sticks" was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA). Results: A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1a, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship. Conclusion: The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies. [ABSTRACT FROM AUTHOR]

Developmental abnormalities and hippocampal aging leads to alteration in cognition. In the brain, N6-methyladenosine (m6 A) is a common and reversible mRNA alteration that is essential for both neurodevelopment and neurodegeneration. However, its function in the postnatal hippocampus and the specific mechanisms regulating hippocampus-related neurodegeneration still awaits elucidate. We identified dynamic m6 A modifications in postnatal hippocampus at different stages (at 10 days postnatally, and at 11 and 64 weeks of age). m6 A shows a definite cell-specific methylation profile and m6 A modification displays temporal dynamic during neurodevelopment and aging. Differentially methylated transcripts in the aged (64-week-old) hippocampus were enriched in microglia. The PD-1/PD-L1 pathways was identified that may participate in the cognitive dysfunction associated with an aged hippocampus. Furthermore, Mettl3 was spatiotemporally expressed in the postnatal hippocampus, which was highly expressed at the age of 11 weeks compared with the other two timepoints. Ectopic expression of METTL3 in mice hippocampus mediated by lentiviral infection resulted in high expression of genes related to PD-1/PD-L1 pathway and significant spatial cognitive deficit. Together, our data show that m6 A dysregulation, which is mediated by METTL3, most likely contributes to cognitive deficits linked to the hippocampus via the PD-1/PD-L1 pathway. [ABSTRACT FROM AUTHOR]

To better understand postprandial glucose metabolic mechanisms in crustaceans, the pathways involved in glucose transport, breakdown, synthesis, and regulation were investigated in the giant freshwater prawn Macrobrachium rosenbergii after feeding. Prawns were fasted for 48 hours and then refed to satiation. Glucose and glycogen contents, along with the transcriptional levels of glucose metabolism-related genes, were measured at 0, 1, 3, 6, and 10 hours after feeding (HAF). Plasma glucose levels peaked at 3 HAF and returned to basal levels by 6–10 HAF. Hepatopancreas glucose followed a similar trend, except for a notable increase at 10 HAF, suggesting gluconeogenesis at this time point. Expression analysis of glucose transporter genes in hepatopancreas revealed a significant upregulation of GLUT1 at 3, 6, and 10 HAF, while GLUT2 showed significant decreases only at 6 HAF. Glycolysis-related genes (GK and PK) exhibited transient increases post-feeding, whereas the gluconeogenesis-related gene FBP was initially suppressed, with expression recovering from 6 HAF onward. The glycogenesis-related gene GS was significantly upregulated at 3, 6, and 10 HAF, correlating with increased glycogen levels in the hepatopancreas. Conversely, the expression of the glycogenolysis-related gene GDE was inhibited after feeding, along with a decrease in the glycogenesis inhibitory gene GSK3. Genes in the insulin signaling pathway (ILP, PI3KCa, and AKT) were upregulated post-feeding, peaking at 3 HAF and subsequently declining. These results suggest that feeding stimulates the insulin signaling pathway and GLUT1 to transport excess glucose, inducing glycolysis and hepatopancreatic glycogenesis, while inhibiting gluconeogenesis and glycogenolysis.

Public servants have faced substantial accountability pressure during the public emergency. It was evident during the pandemic. However, the factors that influence accountability pressure remain to be examined. In this study, we attempt to demonstrate that the Robbins pressure theory provides a useful conceptual framework on how factors affect accountability pressure, and a regression method using primary survey data was applied to investigate how external pressure, the public servants’ capacity, accountability awareness, and communication between superiors and subordinates influence accountability pressure in the fact of a pandemic emergency. The findings show that external pressure had a positive impact on accountability pressure, the public servants’ capacity and communication between superiors and subordinates had a negative impact on accountability pressure, and accountability awareness played a negative moderating role in the effect of external pressure on accountability pressure. This study contributes toward the limited research base, and offers the suggestion that accountability pressure would be alleviated through optimized training and learning.

Abstract In the previous studies, anti‐TGF‐β/PD‐L1 bispecific antibody YM101 is demonstrated, with superior efficacy to anti‐PD‐L1 monotherapy in multiple tumor models. However, YM101 therapy can not achieve complete regression in most tumor‐bearing mice, suggesting the presence of other immunosuppressive elements in the tumor microenvironment (TME) beyond TGF‐β and PD‐L1. Thoroughly exploring the TME is imperative to pave the way for the successful translation of anti‐TGF‐β/PD‐L1 BsAb into clinical practice. In this work, scRNA‐seq is employed to comprehensively profile the TME changes induced by YM101. The scRNA‐seq analysis reveals an increase in immune cell populations associated with antitumor immunity and enhances cell‐killing pathways. However, the analysis also uncovers the presence of immunosuppressive CCR5+ T cells in the TME after YM101 treatment. To overcome this hurdle, YM101 is combined with Maraviroc, a widely used CCR5 antagonist for treating HIV infection, suppressing CCR5+ T cell accumulation, and optimizing the immune response. Mechanistically, YM101‐induced neutrophil activation recruits immunosuppressive CCR5+ T cells via CCR5 ligand secretion, creating a feedback loop that diminishes the antitumor response. Maraviroc then cleared these infiltrating cells and offset YM101‐mediated immunosuppressive effects, further unleashing the antitumor immunity. These findings suggest selectively targeting CCR5 signaling with Maraviroc represents a promising and strategic approach to enhance YM101 efficacy.

Resumo Fundamento A hipertrofia cardíaca patológica (HC) sustentada é um fator de risco independente para aumento da incidência e mortalidade de eventos cardiovasculares. Objetivos Esta pesquisa foi projetada para desvendar o papel do RNA não codificante longo (LncRNA) CCAT2 na progressão da HC. Métodos Procedimentos de constrição aórtica transversal (TAC) foram conduzidos para construir um modelo de HC in vivo induzido por sobrecarga de pressão. O tratamento com angiotensina II (Ang II) foi utilizado para induzir células hipertróficas de cardiomiócitos de rato H9c2. Resultados Os resultados in vivo mostraram que o silenciamento de CCAT2 reduziu a área de superfície dos cardiomiócitos, aliviou a fibrose cardíaca e diminuiu os níveis de β-MHC, ANP e BNP em modelos de camundongos HC. Os resultados in vitro revelaram que o knockdown de CCAT2 reduziu a área de superfície celular e atenuou os níveis de β-MHC, ANP e BNP em células hipertróficas H9c2. Além disso, o silenciamento de CCAT2 diminuiu os níveis de β-catenina ativa, GSK-3β fosforilada e genes alvo Wnt (c-Myc, ciclinaD1 e c-Jun) em camundongos HC e células H9c2 hipertróficas. É importante ressaltar que o tratamento com o ativador da via Wnt / β-catenina LiCl reverteu a supressão do knockdown de CCAT2 na área de superfície celular H9c2 e nos níveis de MHC, ANP e BNP. Conclusões Coletivamente, o silenciamento do CCAT2 desempenha um papel protetor contra a HC através da inativação da sinalização Wnt/β-catenina, o que sugere que o CCAT2 pode se tornar um alvo terapêutico promissor para o HC.

Abstract The Final Year Project (FYP) is one of the most important courses for every undergraduate student, and the effective operation of the FYPs in higher education still faces challenges, such as uneven resource distribution and limited efficiency. This study reports a mixed-methods approach to study the impact of a student-centered FYP allocation mechanism on student performance. This research aims to investigate how aligning students’ FYP choices with their interests can inspire motivation and enhance academic performance. More importantly, this mechanism improves students’ academic resilience, enabling them to navigate unexpected contextual factors. The study’s findings take into account various aspects, including student satisfaction with the allocation process, future improvement methods, and the relationship between interest and context. The outcomes observed in this study support our hypotheses, indicating the improvements in students’ academic performance as well as the pass and completion rates. Moreover, this research contributes to ‘resilience theory’ by exploring students’ adaptability to contextual changes and their enhancement of academic resilience. This study proposes recommendations for cultivating a dynamic student-centered classroom environment. Future work could pay attention to addressing the limitations of this study, exploring other factors influencing FYP allocation, and integrating more quantitative measures for a comprehensive assessment of its impact.

Heat treatment is an important factor affecting the stability of the protein emulsion. This paper investigated the effects of different heat treatment temperature (30, 50, 70, 80 and 90 ℃, 30 min) on the physicochemical properties of tuna protein emulsion. The results showed that the emulsifying property of the heat-treated protein emulsion changed significantly compared with those without heat treatment (P